The objective of this proposal is to understand the basis and biological significance of interactions between corneal cells and trigeminal neurons. Innervation of the cornea during development has been described morphologically, but the basic cellular mechanisms are unknown. Trophic factors appear to have a critical function in neuron-target tissue interactions in numerous systems. Therefore, we will investigate the relationship of trophic factors to the development and maintenance of corneal innervation. Cultures of isolated corneal cells and trigeminal neurons initially will be used to provide more controlled experimental conditions. Previously we have demonstrated the occurrence of a specific epithelial neurontrophic factor (ENF) that prolonged the survival and induced neurite outgrowth of trigeminal neurons. The release of ENF from epithelial cells and its regulation during development and maturation will be studied. The actions of ENF on neurons will be examined on both the cellular and biochemical levels. Culture conditions of epithelial cells will be modified to yield sufficient material to permit purification and further study of the ENF. In addition to studying ENF from cultured corneal cells we intend to examine corneal tissue directly for endogenous trophic activity. The function of retrograde axonal transport in relaying trophic messages from the axonal terminal to the cell soma also will be investigated. Understanding the biochemical events associated with the development of normal corneal innervation will provide the basis for a more rational approach to deal with pathological conditions that disrupt corneal integrity, e.g. recurrent Herpes infections and corneal wounding.